Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A-Bora complex.
J Cell Sci
; 126(Pt 21): 4862-72, 2013 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23970419
ABSTRACT
Pin1 was the first prolyl isomerase identified that is involved in cell division. The mechanism by which Pin1 acts as a negative regulator of mitotic activity in G2 phase remains unclear. Here, we found that Aurora A can interact with and phosphorylate Pin1 at Ser16, which suppresses the G2/M function of Pin1 by disrupting its binding ability and mitotic entry. Our results also show that phosphorylation of Bora at Ser274 and Ser278 is crucial for binding of Pin1. Through the interaction, Pin1 can alter the cytoplasmic translocation of Bora and promote premature degradation by ß-TrCP, which results in a delay in mitotic entry. Together with the results that Pin1 protein levels do not significantly fluctuate during cell-cycle progression and Aurora A suppresses Pin1 G2/M function, our data demonstrate that a gain of Pin1 function can override the Aurora-A-mediated functional suppression of Pin1. Collectively, these results highlight the physiological significance of Aurora-A-mediated Pin1 Ser16 phosphorylation for mitotic entry and the suppression of Pin1 is functionally linked to the regulation of mitotic entry through the Aurora-A-Bora complex.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células
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Fase G2
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Proteínas de Ciclo Celular
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Peptidilprolil Isomerase
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Aurora Quinase A
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Mitose
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article